Wound healing in tissues is a complex reparative process. Under normal circumstances, the process of acute wound healing can be broken down into three phases. An initial inflammatory phase, which is followed by robust tissue remodeling and proliferation (the proliferative phase), is succeeded by a maturational phase wherein re-epithelialization, dermal angiogenesis and wound closure ensues. Re-epithelialization involves the migration and proliferation of epithelial tissue, primarily keratinocytes. Angiogenesis is the growth of new blood vessels from pre-existing conduits, and is regulated by a panoply of soluble cytokines including growth factor polypeptides, as well as cell-cell and cell-matrix interactions. Chronic wounds exhibit a different healing profile from normal acute wounds in that they generally remain in an inflamed state for protracted periods of time. Non-healing wounds can most commonly be observed amongst people with diabetes, venous stasis disease, and in those patients who are immobilized. In view of the foregoing, it would be desirable to provide new biomolecules that safely and efficiently potentiate epithelial and vascular wound healing mechanisms in both acute and chronic wound healing situations. Drugs for promoting wound healing have been recently developed such as Beclapermin, a genetically engineered recombinant PDGF from Johnson & Johnson, or a pharmaceutical composition for regeneration and repair of mammalian tissues comprising PDGF and dexamethasone (EP0575484). U.S. Pat. No. 5,981,606 discloses a wound healing agent comprising TGF-beta and U.S. Pat. No. 6,800,286 and U.S. Pat. No. 5,155,214 disclose wound healing agents comprising FGF.
All already described healing agents are growth factors, cytokines or chemokines, collagen or hyaluronic acid. These agents present the drawback of inducing adverse events as they are not specific of one cellular type.
There is still a need for an alternative wound healing agent that results in an effective and rapid wound healing and does not cause adverse events.
The present invention aims to provide new peptides as alternative wound healing agent, said peptides being specific of the angiogenesis mediated by endothelial cells. Peptides, which are less than 50 amino acids, present the advantage of being an interesting tool for therapeutic use due to their small size: they offer a high affinity-specificity to their target and low toxicity profiles, a room temperature storage and better tissue penetration owing to their smaller size.
Moreover, they present the advantage of being easily synthesized compared to a full-length protein: their industrial production is thus more standardized and controlled. They do not show viral security issue as they can be chemically synthesized and do not suffer from refolding issues, glycosylation issues and activity variability.